Neuro-immune regulation of macromolecular permeability in the normal human colon and in ulcerative colitis

Persistent stress and life events affect the course of ulcerative colitis (UC) by largely unknown mechanisms. Regulation of epithelial permeability to antigens is crucial for the balance between inflammation and immuno-surveillance, and increased intestinal permeability has been shown in patients with ulcerative colitis. Corticotropin releasing hormone (CRH) has been implicated as an important mediator of stress-induced abnormalities in intestinal mucosal function in animal models. Further cholinergic signalling during stress has been reported to increase bowel ion secretion in humans and uptake of HRP in rodents via activation of mast cells.

The overall aim: of this thesis was to examine the role of CRH-mediated and cholinergic signalling, and their interaction with mast cells and eosinophils, in the regulation of the mucosal barrier function in the normal human colon and in UC. In vivo studies or the use of surgical specimens for such studies have major shortcomings. Therefore a method with endoscopic biopsies in Ussing chambers was established for studies of protein antigen uptake and electrophysiology in human colonic biopsies, and used in subsequent investigations…

Contents

1. INTRODUCTION
Ulcerative colitis
Aetiology
Treatment
2. BACKGROUND TO THE STUDY
Structure of the large intestine
Colonic barrier function
Uptake and transport
Stress
3. AIMS OF THE THESIS
4. SUBJECTS AND METHODOLOGY
Volunteers and patients
Methodological considerations I
Ussing chamber experiments
Methodological considerations II
Histology
Methodological considerations III
Statistics
5. RESULTS
PAPER I
PAPER II
PAPER III
PAPER IV
6. DISCUSSION
7. CONCLUSIONS
8. TACK
9. SVENSK SAMMANFATTNING
10. REFERENCES

Author: Wallon, Conny

Source: Linkoping University

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